Expression QTL mapping in regulatory and helper T cells from the BXD family of strains reveals novel cell-specific genes, gene-gene interactions and candidate genes for auto-immune disease
- Equal contributors
1 Department of Infection Genetics, Helmholtz Centre for Infection Research & University of Veterinary Medicine Hannover, Inhoffenstr. 7, D-38124 Braunschweig, Germany
2 Research Group Immune Regulation, Helmholtz Centre for Infection Research, Inhoffenstr. 7, D-38124 Braunschweig, Germany and Research Group Infection Immunology, Department of Medical Microbiology, Otto-von-Guericke-University Magdeburg, Leipziger Straße 44, D-39120 Magdeburg, Germany
3 Department of Molecular and Cellular Neurobiology, Center for Neuroscience and Cognitive Research, Neuroscience Campus Amsterdam, VU University, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands
4 Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, Tennessee, USA
5 Research Group Genome Analytics, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany
BMC Genomics 2011, 12:610 doi:10.1186/1471-2164-12-610Published: 19 December 2011
Regulatory T cells (Tregs) play an essential role in the control of the immune response. Treg cells represent important targets for therapeutic interventions of the immune system. Therefore, it will be very important to understand in more detail which genes are specifically activated in Treg cells versus T helper (Th) cells, and which gene regulatory circuits may be involved in specifying and maintaining Treg cell homeostasis.
We isolated Treg and Th cells from a genetically diverse family of 31 BXD type recombinant inbred strains and the fully inbred parental strains of this family--C57BL/6J and DBA/2J. Subsequently genome-wide gene expression studies were performed from the isolated Treg and Th cells. A comparative analysis of the transcriptomes of these cell populations allowed us to identify many novel differentially expressed genes. Analysis of cis- and trans-expression Quantitative Trait Loci (eQTLs) highlighted common and unique regulatory mechanisms that are active in the two cell types. Trans-eQTL regions were found for the Treg functional genes Nrp1, Stat3 and Ikzf4. Analyses of the respective QTL intervals suggested several candidate genes that may be involved in regulating these genes in Treg cells. Similarly, possible candidate genes were found which may regulate the expression of F2rl1, Ctla4, Klrb1f. In addition, we identified a focused group of candidate genes that may be important for the maintenance of self-tolerance and the prevention of allergy.
Variation of expression across the strains allowed us to find many novel gene-interaction networks in both T cell subsets. In addition, these two data sets enabled us to identify many differentially expressed genes and to nominate candidate genes that may have important functions for the maintenance of self-tolerance and the prevention of allergy.